Type 1 invariant natural killer T cell (iNKT) (iNKT)

Type 1 invariant natural killer T (iNKT) cells are a specialized subset of T lymphocytes that bridge the innate and adaptive immune systems by expressing a semi-invariant T-cell receptor (TCR) and natural killer (NK) cell markers (NIH, 2012). In humans, the iNKT TCR is characterized by the Vα24-Jα18 chain paired with Vβ11, which recognizes glycolipid antigens presented by the non-polymorphic MHC class I-like molecule CD1d (Frontiers in Immunology, 2024). Upon activation by agonists such as alpha-galactosylceramide (α-GalCer), iNKT cells rapidly secrete large quantities of cytokines, including interferon-gamma (IFN-γ) and interleukin-4 (IL-4), which activate NK cells, dendritic cells, and conventional T cells (Ash Publications, 2012; Oncodaily, 2025). These cells play a critical role in tumor immunosurveillance, defense against pathogens, and the regulation of autoimmune and inflammatory diseases (NIH, 2012; Cardiovascular Research, 2016). Therapeutically, iNKT cells are being explored as targets for synthetic glycolipid agonists and as platforms for chimeric antigen receptor (CAR) cell therapies (NCI, 2025; Frontiers in Immunology, 2024). However, challenges such as iNKT cell anergy and the risk of cytokine release syndrome remain significant considerations in their clinical development (Soton, 2015; Frontiers in Immunology, 2024).

Other names

Invariant natural killer T cellType I NKT celliNKT cellVα24-Jα18 NKT cellCD1d-restricted NKT cell

iNKT cell agonists, such as alpha-galactosylceramide, bind to the CD1d molecule on antigen-presenting cells to form a complex that is specifically recognized by the invariant T-cell receptor (TCR) on iNKT cells (NIH, 2012). This interaction triggers rapid activation and the secretion of a broad spectrum of Th1 and Th2 cytokines, such as interferon-gamma and interleukin-4, which subsequently activate natural killer (NK) cells, dendritic cells, and cytotoxic T lymphocytes to mediate antitumor or antimicrobial effects (Frontiers in Immunology, 2024).